Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Sarcopenia Trials in Specific Diseases: Report by the International Conference on Frailty and Sarcopenia Research Task Force.

Muscle atrophy occurs as a consequence of a number of conditions, including cancer, chronic obstructive pulmonary disease (COPD), diabetes mellitus, heart failure, and other chronic diseases, where it is generally a predictor of poor survival. It also occurs as a consequence of disuse and an age-related loss of muscle mass and strength (sarcopenia). The aims of the 2016, International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force were to examine how these specific chronic conditions have been employed in treatment trials thus far and how future trials using these patient groups might be designed for efficient identification of effective sarcopenia interventions. Functional limitations assessed as gait speed, distance walked over a set time period, or other attributes of physical performance have been suggested as outcome measures in sarcopenia trials. Indeed, such measures have already been used successfully in a number of trials aimed at preventing disability in older adults.

PHARMACOLOGICAL INTERVENTIONS IN FRAILTY AND SARCOPENIA: REPORT BY THE INTERNATIONAL CONFERENCE ON FRAILTY AND SARCOPENIA RESEARCH TASK FORCE.

Sarcopenia and frailty often co-exist and both have physical function impairment as a core component. Yet despite the urgency of the problem, the development of pharmaceutical therapies for sarcopenia and frailty has lagged, in part because of the lack of consensus definitions for the two conditions. A task force of clinical and basic researchers, leaders from the pharmaceutical and nutritional industries, and representatives from non-profit organizations was established in 2012 with the aim of addressing specific issues affecting research and clinical activities on frailty and sarcopenia. The task force came together on April 22, 2015 in Boston, Massachusetts, prior to the International Conference on Frailty and Sarcopenia Research (ICFSR). The theme of this meeting was to discuss challenges related to drugs designed to target the biology of frailty and sarcopenia as well as more general questions about designing efficient drug trials for these conditions. The present article reports the results of the task force's deliberations based on available evidence and preliminary results of ongoing activities. Overall, the lack of a consensus definition for sarcopenia and frailty was felt as still present and severely limiting advancements in the field. However, agreement appears to be emerging that low mass alone provides insufficient clinical relevance if not combined with muscle weakness and/or functional impairment. In the next future, it will be important to build consensus on clinically meaningful functional outcomes and test/validate them in long-term observational studies.

The mobility gap between older men and women: the embodiment of gender.

OBJECTIVES: To present the study design and baseline results of the longitudinal International Mobility in Aging Study (IMIAS) on gender differences in physical performance and mobility disability prevalence in five diverse societies. METHODS: Data are from surveys on random samples of people aged 65-74 years at Canadian (Kingston, Ontario; Saint-Hyacinthe, Quebec), Mediterranean (Tirana, Albania) and Latin American sites (Natal, Brazil; Manizales, Colombia) (N=1995). Mobility disability was defined as reporting difficulty in walking 400m or climbing stairs. Activities of daily living (ADL) disability was based on any self-reported difficulty in five mobility-related ADLs. The short physical performance battery (SPPB) was used to assess physical performance. Poisson regression models were fitted to estimate prevalence ratios. RESULTS: Age-adjusted prevalence of low SPPB, mobility disability and ADL disability were higher in women than in men in all sites except for Kingston. After adjustment for education and income, gender differences in SPPB and ADL disability attenuated or disappeared in Saint-Hyacinthe and Manizales but remained large in Tirana and Natal and mobility disability remained more frequent in women than in men at all sites except Kingston. After further adjustment by chronic conditions and depressive symptoms, gender differences in mobility remained large at all sites except Kingston but only in Tirana did women have significantly poorer physical performance than men. DISCUSSION: Results provide evidence for gender as a risk factor to explain poorer physical function in women and suggest that moving toward gender equality could attenuate the gender gap in physical function in old age.

The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).

OBJECTIVE: To determine if sarcopenia modulates the response to a physical activity intervention in functionally limited older adults. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Three academic centers. PARTICIPANTS: Elders aged 70 to 89 years at risk for mobility disability who underwent dual-energy x-ray absorptiometry (DXA) for body composition at enrollment and follow-up at twelve months (N = 177). INTERVENTION: Subjects participated in a physical activity program (PA) featuring aerobic, strength, balance, and flexibility training, or a successful aging (SA) educational program about healthy aging. MEASUREMENTS: Sarcopenia as determined by measuring appendicular lean mass and adjusting for height and total body fat mass (residuals method), Short Physical Performance Battery score (SPPB), and gait speed determined on 400 meter course. RESULTS: At twelve months, sarcopenic and non-sarcopenic subjects in PA tended to have higher mean SPPB scores (8.7±0.5 and 8.7±0.2 points) compared to sarcopenic and non-sarcopenic subjects in SA (8.3±0.5 and 8.4±0.2 points, p = 0.24 and 0.10), although the differences were not statistically significant. At twelve months, faster mean gait speeds were observed in PA: 0.93±0.4 and 0.95±0.03 meters/second in sarcopenic and non-sarcopenic PA subjects, and 0.89±0.4 and 0.91±0.03 meters/second in sarcopenic and non-sarcopenic SA subjects (p = 0.98 and 0.26), although not statistically significant. There was no difference between the sarcopenic and non-sarcopenic groups in intervention adherence or number of adverse events. CONCLUSION: These data suggest that older adults with sarcopenia, who represent a vulnerable segment of the elder population, are capable of improvements in physical performance after a physical activity intervention.

Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations.

An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials.

Diet quality and social support: factors associated with serum carotenoid concentrations among older disabled women (the Women's Health and Aging Study).

PURPOSE: This study investigated the relationship between social support (including instrumental support, emotional support, social interaction, social space, and family networks) and diet quality, as indicated by serum carotenoid levels. DESIGN AND METHODS: The sample consisted of participants in the Women's Health and Aging Study with longitudinal carotenoid data (n=325). We performed regression analyses using baseline indicators of social support and changes in social support to determine whether baseline levels and/or change in levels of social support predict changes in serum carotenoid levels. Social support changes were measured over 1 year from baseline to follow-up round 1. Carotenoid level changes were established from follow-up round 1 to round 2. To determine whether or not regression to the mean was driving these results, we performed an analysis that included baseline and change levels of social support indicators. RESULTS: At baseline, the frequency of leaving one's home was associated with a decrease in carotenoid levels. Leaving one's home more frequently predicted an increase in carotenoid levels and attending fewer activities predicted a decrease in carotenoid levels. IMPLICATIONS: In older, community-resident disabled women, baseline levels of social support did not consistently predict diet quality. However, change in social support predicted both positive and negative change in diet quality and thus provides supportive evidence that social activity and family interaction may play meaningful roles in the maintenance of diet quality among functionally compromised older women. Further research is necessary to more fully understand the impact of multiple forms of social supports on the diet quality of older adults.

Potential Prognostic Value of Handgrip Strength in Older Hospitalized Patients.

OBJECTIVES: Objective measures of physical function are useful prognostic tools also for hospitalized elders. Low handgrip strength is predictive of poor outcomes and it can be assessed also in a sitting position, representing a potential alternative measure in bedridden patients. We evaluated grip strength prognostic value in hospitalized older patients. DESIGN: Prospective cohort study. SETTING: Geriatric, medical ward of an academic medical center in Ferrara, Italy. PARTICIPANTS: Patients aged 65 and older (N = 88) admitted to the hospital for an acute medical condition. MEASUREMENTS: Patients were evaluated for grip strength at hospital admission and were re-evaluated at discharge. After discharge, they were followed every 3 months for 1 year by telephone interviews to assess new hospitalizations and vital status. RESULTS: The mean age of the sample was 77.3 years, 47% were women. At admission, mean height standardized handgrip strength was 15.7±5 kg/m; men had greater strength (p<0.001). There was a direct relationship of admission grip strength with BMI (p<0.05), serum albumin (p=0.07), and Short Physical Performance Battery score (p<0.05), and an inverse relationship with age (gender-adjusted p value <0.01). In multiple regression analysis, after adjustment for possible confounders, patients in third tertile of grip strength had a shorter hospital stay compared to those in the first tertile (ß -2.8; p<0.05). Patients with higher grip strength at discharge also had a lower risk of rehospitalization or death over the follow-up, although the result was not statistically significant (OR: 0.68; 95% CI: 0.30-1.52). CONCLUSION: In older hospitalized medical patients, grip strength assessment might provide useful prognostic information.

The hormonal profile of hip fracture female patients differs from community-dwelling peers over a 1-year follow-up period.

UNLABELLED: Hormone levels were compared over a 1-year period between elderly women who had sustained a hip fracture and women of similar age and functional ability. Our study suggests progressive hormonal changes that may contribute to severe bone loss during the year following hip fracture. INTRODUCTION: Alterations in hormones affecting the musculoskeletal system may increase risk of hip fracture or poor post-fracture recovery in postmenopausal women. Most studies lack appropriate reference groups, and thus cannot assess the extent to which these alterations are attributable to hip fracture. METHODS: Women aged ≥65 years hospitalized for an acute hip fracture (Baltimore Hip Studies, BHS-3; n = 162) were age-matched to 324 women enrolled in the Women's Health and Aging Study I, a Baltimore-based cohort with similar functional status to the pre-fracture status of BHS-3 women. Both studies enrolled participants from 1992 to 1995. Insulin-like growth hormone-1 (IGF-1), parathyroid hormone (PTH), 1,25 dihydroxyvitamin D [1,25(OH)2D], and osteocalcin were evaluated at baseline and 2, 6, and 12 months post-fracture, and at baseline and 12 months in the comparison group. Between-group differences in trajectories of each hormone were examined. RESULTS: Baseline mean IGF-1 levels were significantly lower in hip fracture patients than the comparison group (75.0 vs. 110.5 µg/dL; p < 0.001). Levels increased by 2 months post-fracture, but remained significantly lower than those in the comparison group throughout the 12-month follow-up (p < 0.01). Levels of PTH and osteocalcin were similar between groups at baseline, but rose during the year post-fracture to significantly differ from the comparison women (p < 0.001). 1,25(OH)2D levels did not differ between the hip fracture and comparison women at any time. CONCLUSIONS: Older women who have sustained a hip fracture have progressive changes in hormonal milieu that exceed those of women of similar health status during the year following fracture.

High sensitivity C-reactive protein predicts the development of new carotid artery plaques in older persons.

BACKGROUND AND AIM: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated. METHODS AND RESULTS: 486 "InCHIANTI" Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5-1.9) and 1.9 (95%CI 1.2-3.1), respectively. Participants with high (>3 µg/mL) and moderate (≥1 and ≤3 µg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9-2.6) and 1.9 (95%CI 1.6-2.3) respectively, when compared with subjects with low (<1 µg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques. CONCLUSIONS: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.

Relationship between low levels of high-density lipoprotein cholesterol and dementia in the elderly. The InChianti study.

BACKGROUND: To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals. METHODS: A total of 1051 older community-dwelling individuals (age >/=65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years. RESULTS: At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle-brachial index. CONCLUSIONS: Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels.

Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults.

BACKGROUND/OBJECTIVES: Vitamin D deficiency is associated with cardiovascular disease, osteoporosis, poor muscle strength, falls, fractures and mortality. Although older adults are at a higher risk of vitamin D deficiency, the relationship of serum 25-hydroxyvitamin D (25(OH)D) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly. We hypothesized that low serum 25(OH)D levels predicted mortality in older adults. SUBJECTS/METHODS: Serum 25(OH)D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults, aged > or =65 years, who participated in the InCHIANTI (Invecchiare in Chianti, Aging in the Chianti Area) study, a population-based, prospective cohort study of aging in Tuscany, Italy. Serum 25(OH)D levels were measured at the time of enrollment in 1998-1999, and participants were followed up for mortality. RESULTS: During 6.5 years of follow-up, 228 (22.7%) participants died, of whom 107 died due to cardiovascular diseases. Compared with participants in the highest quartile of serum 25(OH)D (>26.5 ng/ml) (to convert to nmol/l, multiply by 2.496), those in the lowest quartile (<10.5 ng/ml) had increased risk of all-cause mortality (Hazard Ratio (H.R.) 2.11, 95% Confidence Interval (95% C.I.): 1.22-3.64, P=0.007) and cardiovascular disease mortality (H.R. 2.64, 95% C.I.: 1.14-4.79, P=0.02), in multivariate Cox proportional hazards models that adjusted for age, sex, education, season, physical activity and other potential confounders. CONCLUSIONS: Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality.

Basic ADL disability and functional limitation rates among older AMERICANS from 2000-2005: the end of the decline?

BACKGROUND: This study sought to determine whether the rates of basic activities of daily living (ADL) disabilities and functional limitations declined, remained the same, or increased between 2000 and 2005 when (a) only community-dwelling Americans aged 65 and older were examined and (b) when institutionalized older adults were included. METHOD: Using data from the American Community Survey and the National Nursing Home Survey, we calculated annual prevalence rates of basic ADL disabilities and functional limitations and fitted regression lines to examine trends over time. RESULTS: The rates of basic ADL disabilities among community-dwelling adults aged 65 and older increased 9% between 2000 and 2005. When institutionalized elders were included, basic ADL disability rates were stable among men but increased among women. Functional limitation rates did not significantly change between 2000 and 2005. CONCLUSION: These findings suggest an end of the decline in disability rates among older Americans, which, if confirmed, could have important implications for health care.

Patterns in trouble sleeping among women at mid-life: results from a British prospective cohort study.

BACKGROUND: Although trouble sleeping is a common problem among women at mid-life, patterns in trouble sleeping relating to social and health-related risk factors are unclear. This analysis describes the dynamics of trouble sleeping among women at mid-life. METHODS: The National Survey of Health and Development is a nationally representative study of births in 1946 in England, Scotland, and Wales followed up through mid-life. Multistate life table analysis utilised 893 women interviewed annually between ages 48 to 54 years. RESULTS: Women spent an average of 2.6 years with trouble sleeping, and the average length of a continuous episode of trouble sleeping was 2.4 years. Among women who reported at least one episode, the average number of episodes was 1.5. Health-related risk factors at age 43 of number of physical conditions, anxiety and depression symptoms, use of prescription medication, and current or past trouble sleeping were related to increased total and per episode duration of trouble sleeping over the 7-year study interval and increased duration per episode. Differences associated with these risk factors ranged from 1.2 to 1.8 years for duration over the study interval and 0.5 to 0.8 years per episode. There was no association between average number of episodes per woman reporting at least one episode and these health-related risk factors at age 43. CONCLUSIONS: This study provides support for association between increased duration of trouble sleeping, in total and per episode, and health risk factors at age 43, suggesting a long-term relationship between risk factors and sleep.

The effect of obesity combined with low muscle strength on decline in mobility in older persons: results from the InCHIANTI study.

OBJECTIVE: Both obesity and muscle impairment are increasingly prevalent among older persons and negatively affect health and physical functioning. However, the combined effect of coexisting obesity and muscle impairment on physical function decline has been little studied. We examined whether obese persons with low muscle strength experience significantly greater declines in walking speed and mobility than persons with only obesity or low muscle strength. DESIGN: Community-dwelling adults aged > or = 65 years (n = 930) living in the Chianti geographic area (Tuscany, Italy) were followed for 6 years in the population-based InCHIANTI study. MEASUREMENTS: On the basis of baseline measurements (1998-2000), obesity was defined as body mass index (BMI) > or = 30 kg/m(2) and low muscle strength as lowest sex-specific tertile of knee extensor strength. Walking speed and self-reported mobility disability (ability to walk 400 m or climb one flight of stairs) were assessed at baseline and at 3- and 6-year follow-up. RESULTS: At baseline, obese persons with low muscle strength had significantly lower walking speed compared with all other groups (P < or = 0.05). In longitudinal analyses, obese participants with low muscle strength had steeper decline in walking speed and high risk of developing new mobility disability over the 6-year follow-up compared with those without obesity or low muscle strength. After the age of 80, the differences between groups were substantially attenuated. The differences seen in walking speed across combination of low muscle strength and obesity groups were partly explained by 6-year changes in muscle strength, BMI and waist circumference. CONCLUSIONS: Obesity combined with low muscle strength increases the risk of decline in walking speed and developing mobility disability, especially among persons < 80 years old.

Low serum selenium is associated with anemia among older adults in the United States.

OBJECTIVE: We hypothesized that low serum selenium was associated with anemia in humans. SUBJECTS: A total of 2092 adults aged 65 and older, in the third National Nutrition Examination Survey, Phase 2 (1991-1994) (NHANES III). METHODS: Examination of the relationship between serum selenium and hematological indices in NHANES III. RESULTS: Anemia, defined by World Health Organization criteria, was present in 12.9%. Mean serum selenium among non-anemic and anemic adults was 1.60 and 1.51 micromol l(-1) (P=0.0003). The prevalence of anemia among adults in the lowest to highest quartiles of serum selenium was 18.3, 9.5, 9.7 and 6.9%, respectively (P=0.0005). The proportion of adults in the lowest quartile of selenium among those who were non-anemic or who had anemia due to nutritional causes, chronic inflammation, renal disease or unexplained anemia was 9.9, 27.5, 17.5, 24.0 and 15.4%, respectively. An increase in log(e) selenium was associated with a reduced risk of anemia (odds ratio per one standard deviation increase 0.75, 95% confidence interval 0.58-0.97, P=0.03), adjusting for age, race, education, body mass index and chronic diseases. CONCLUSION: Low serum selenium is independently associated with anemia among older men and women in the United States.

Sex hormone binding globulin levels across the adult lifespan in women--the role of body mass index and fasting insulin.

SHBG is a major carrier of androgens. In men, SHBG levels increase with age, while in women data are scant. There is evidence that body mass index (BMI) and fasting insulin influence SHBG concentration. Since low SHBG levels are predictors of insulin resistance and diabetes, understanding the relationship of SHBG with age, insulin, and BMI is important to gain insight into the role of SHBG as a cardiovascular risk factor in women. Differences in SHBG across adult life span and their relationship with insulin and BMI were evaluated in a representative cohort of 616 Italian women free of diabetes and not on hormone replacement therapy enrolled in the InCHIANTI Study. The relationship of SHBG with age, BMI, and fasting insulin levels was analyzed using linear regression and by loess smoother. Serum SHBG levels showed a U-shaped trajectory with age, declining from the 2nd to the 6th decade of life and increasing after the 6th decade (p<0.0001). Age-related trends for BMI and fasting insulin mirrored the trend observed for SHBG. After adjusting for fasting insulin, the relationship between log (SHBG) and age square was attenuated (beta coefficient from 0.00044 to 0.00039) and was further reduced after adjustment for BMI (from 0.00039 to 0.00028). SHBG levels show an age-related U-shaped trajectory. These changes mirror the age-related changes in BMI and fasting insulin, suggesting that BMI and insulin negatively influence SHBG concentration.

Characterisation of smoking behaviour across the life course and its impact on decline in lung function and all-cause mortality: evidence from a British birth cohort.

OBJECTIVES: To describe smoking trajectories from early adolescence into mid-life and to examine the effects of these trajectories on health and all-cause mortality. METHODS: A nationally representative birth cohort study including 3387 men and women followed up since their birth in 1946 in England, Scotland and Wales. The main outcome measure is all-cause mortality by age 60 years and rate of decline in forced expiratory volume in 1 second (FEV(1)). RESULTS: Eighteen per cent of the sample were categorised as lifelong smokers (smokers at all six waves at ages 20, 25, 31, 36, 43, 53 years), of whom 90% had begun smoking by age 18 years. By age 60 years, 10% of all lifelong smokers had died. They had a threefold increase in mortality rate compared with never smokers (hazard ratio (HR) 3.2, 95% confidence interval (CI) 2.1 to 4.8). For predominantly smokers (smokers for at least four of the six data collections), mortality rate remained higher than never smokers (HR 1.6, 95% CI 1.0 to 2.5). Predominantly non-smokers did not differ from those who never smoked (HR 1.3, 95% CI 0.9 to 2.0). Using the most recent smoking status available, current smokers had more than double the risk of mortality compared with never smokers (HR 2.4, 95% CI 1.6 to 3.5). Lifelong smokers and predominantly smokers had a greater rate of decline in lung function than never smokers (regression coefficients -18 ml/year, 95% CI -22 to -13; -6, 95% CI -10.3 to -1.7 respectively). For current smokers, the decline was 8.4 ml/year (95% CI -12.0 to -5.0) faster than never smokers. CONCLUSIONS: The strength and differentiation of adverse effects identified by using simplified smoking behaviours has highlighted the advantages of obtaining further information on lifelong smoking behaviour from former smokers, rather than just current smoking status.